Combinatorial methods to improve the therapeutic benefit of bisantrene and analogs and derivatives thereof
Inventors
Garner, William J. • Franklin, Arnie • Rothman, John
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11147800-B2
Publication Date
2021-10-19
Expiration Date
Abstract
The present invention describes methods and compositions for improving the therapeutic efficacy of therapeutic agents previously limited by suboptimal therapeutic performance by either improving efficacy as monotherapy or reducing side effects. Such methods and compositions are particularly applicable to bisantrene or derivatives, analogs, or prodrugs thereof.
Core Innovation
The invention provides a method to improve the efficacy and/or reduce the side effects of suboptimally administered drug therapy by identifying at least one factor or parameter associated with the efficacy and/or occurrence of side effects, and by modifying that factor or parameter. The drug therapy comprises administration of bisantrene or a salt or prodrug of bisantrene. The method is framed to address suboptimal drug therapy performance in cancer and related proliferative conditions.
The factor or parameter is associated with at least one of the specific disease or condition being treated, the stage of the disease or condition being treated, selection of an appropriate patient for treatment, selection of an appropriate phenotype of the patient or the disease or condition being treated, the chemical composition of the drug, the physical form of the drug or pharmaceutical composition, the makeup of the pharmaceutical composition, the specific use of the drug being administered, the target cell, organ, or receptor targeted by the drug being administered, or additional agents administered with the drug being administered.
In embodiments, the framework includes patient or disease phenotype and/or genotype, including biomarker/assay selections and genetic/SNP-related determinations associated with sensitivity and resistance to bisantrene. The disclosure also includes modifying dosing regimens and schedules, employing drug delivery systems, and using drug combinations and adjunct components, including immunoactivity-inducing agents, macrophage activation, cytokines, antibodies, innate/adaptive immune stimulators, checkpoint inhibitors, other targeted agents, conventional cytotoxics, and verapamil.
Claims Coverage
The document discloses independent claims covering a method to improve the efficacy and/or reduce the side effects of suboptimally administered drug therapy by identifying and modifying at least one factor or parameter associated with efficacy and/or side effects, with the therapy comprising administration of bisantrene or a salt or prodrug. The claims combine a general identification-and-modification framework with specific categories of associated factors or parameters and several dependent refinements.
Identify and modify efficacy/side-effect factor or parameter
Identifying at least one factor or parameter associated with the efficacy and/or occurrence of side effects of the drug therapy, and modifying the factor or parameter to improve the efficacy and/or reduce the side effects of the drug therapy.
Disease, stage, patient, or phenotype association
The factor or parameter is additionally associated with at least one of the specific disease or condition being treated, the stage of the disease or condition being treated, selection of an appropriate patient for treatment, or selection of an appropriate phenotype of the patient or the disease or condition being treated.
Chemical composition, physical form, use, target, or additional agents
The factor or parameter is additionally associated with at least one of the chemical composition of the drug being administered, the physical form of the drug or pharmaceutical composition, the makeup of the pharmaceutical composition, the specific use of the drug being administered, the target cell, organ, or receptor targeted by the drug being administered, or additional agents administered with the drug being administered.
Bisantrene-based drug therapy
The drug therapy comprises administration of bisantrene or a salt or prodrug of bisantrene.
Dose and schedule modification refinements
Selecting dose modification and schedule formats, including administration schedule formats, intermittent or daily administration, and schedules to avoid anaphylaxis.
Drug delivery system selection
Using a drug delivery system or carrier system, including nanoparticles, liposomes, and nonpegylated liposomes.
Multidrug resistance reversal with verapamil
Using the method in combination with verapamil as a multidrug resistance reversal agent.
The claims are directed to improving efficacy and/or reducing side effects of suboptimally administered drug therapy by identifying and modifying an associated factor or parameter, applied to bisantrene or a salt or prodrug. The inventive features further include patient and disease associations, formulation and use associations, dose and schedule refinements, delivery system selection, and verapamil combination therapy.
Stated Advantages
Improve the efficacy of suboptimally administered drug therapy.
Reduce the side effects of suboptimally administered drug therapy.
Documented Applications
Treatment of cancer using bisantrene or a salt or prodrug of bisantrene.
Treatment of ovarian cancer, refractory breast cancer, triple-negative breast cancer, acute myelocytic leukemia, and acute leukemias of childhood.
Cancer and non-malignant proliferative conditions described as applicable via bisantrene-based combinatorial regimens and factor/parameter modification.
Selecting patients and/or analyzing patient or disease phenotype or genotype to improve efficacy and/or reduce side effects of bisantrene-based therapy.
Using drug-composition, physical form, target, and co-administered agent factors to improve efficacy and/or reduce side effects of bisantrene-based therapy.
Interested in licensing this patent?